Efficacy of bright light and sleep/darkness scheduling in alleviating circadian maladaptation to night work.
We tested the hypothesis that circadian adaptation to night work is best achieved by combining bright light during the night shift and scheduled sleep in darkness. Fifty-four subjects participated in a shift work simulation of 4 day and 3 night shifts followed by a 38-h constant routine (CR). Subjects received 2,500 lux (Bright Light) or 150 lux (Room Light) during night shifts and were scheduled to sleep (at home in darkened bedrooms) from 0800 to 1600 (Fixed Sleep) or ad libitum (Free Sleep). Dim light melatonin onset (DLMO) was measured before and after the night shifts. Both Fixed Sleep and Bright Light conditions significantly phase delayed DLMO. Treatments combined additively, with light leading to larger phase shifts. Free Sleep subjects who spontaneously adopted consistent sleep schedules adapted better than those who did not. Neither properly timed bright light nor fixed sleep schedules were consistently sufficient to shift the melatonin rhythm completely into the sleep episode. Scheduling of sleep/darkness should play a major role in prescriptions for overcoming shift work-related phase misalignment. (+info)
beta(1)-adrenergic antagonists improve sleep and behavioural disturbances in a circadian disorder, Smith-Magenis syndrome.
Smith-Magenis syndrome (SMS) is a clinically recognisable contiguous gene syndrome ascribed to interstitial deletions of chromosome 17p11.2. Patients have a phase shift of their circadian rhythm of melatonin with a paradoxical diurnal secretion of the hormone. Serum melatonin levels and day-night behaviour were studied in nine SMS children (aged 4 to 17 years) given acebutolol, a selective beta(1)-adrenergic antagonist (10 mg/kg early in the morning). Cardiac examination, serum melatonin, motor activity recordings, and sleep diaries were monitored before and after drug administration. The present study shows that a single morning dose of acebutolol suppressed the inappropriate secretion of melatonin in SMS. A significant improvement of inappropriate behaviour with increased concentration, delayed sleep onset, increased hours of sleep, and delayed waking were also noted. These results suggest that beta(1)-adrenergic antagonists help to manage hyperactivity, enhance cognitive performance, and reduce sleep disorders in SMS. (+info)
Hypothalamic involvement in chronic migraine.
OBJECTIVES: Chronic migraine (CM), previously called transformed migraine, is a frequent headache disorder that affects 2%-3% of the general population. Analgesic overuse, insomnia, depression, and anxiety are disorders that are often comorbid with CM. Hypothalamic dysfunction has been implicated in its pathogenesis, but it has never been studied in patients with CM. The aim was to analyze hypothalamic involvement in CM by measurement of melatonin, prolactin, growth hormone, and cortisol nocturnal secretion. METHODS: A total of 338 blood samples (13/patient) from 17 patients with CM and nine age and sex matched healthy volunteers were taken. Melatonin, prolactin, growth hormone, and cortisol concentrations were determined every hour for 12 hours. The presence of comorbid disorders was also evaluated. RESULTS: An abnormal pattern of hypothalamic hormonal secretion was found in CM. This included: (1) a decreased nocturnal prolactin peak, (2) increased cortisol concentrations, (3) a delayed nocturnal melatonin peak in patients with CM, and (4) lower melatonin concentrations in patients with CM with insomnia. Growth hormone secretion did not differ from controls. CONCLUSION: These results support hypothalamic involvement in CM, shown by a chronobiologic dysregulation, and a possible hyperdopaminergic state in patients with CM. Insomnia might be an important variable in the study findings. (+info)
Heart rate and energy expenditure of incubating wandering albatrosses: basal levels, natural variation, and the effects of human disturbance.
We studied the changes in heart rate (HR) associated with metabolic rate of incubating and resting adult wandering albatrosses (Diomedea exulans) on the Crozet Islands. Metabolic rates of resting albatrosses fitted with external HR recorders were measured in a metabolic chamber to calibrate the relationship between HR and oxygen consumption (V(O(2))) (V(O(2))=0.074 x HR+0.019, r(2)=0.567, P<0.001, where V(O(2)) is in ml kg(-1) min(-1) and HR is in beats min(-1)). Incubating albatrosses were then fitted with HR recorders to estimate energy expenditure of albatrosses within natural field conditions. We also examined the natural variation in HR and the effects of human disturbance on nesting birds by monitoring the changes in HR. Basal HR was positively related to the mass of the individual. The HR of incubating birds corresponded to a metabolic rate that was 1.5-fold (males) and 1.8-fold (females) lower than basal metabolic rate (BMR) measured in this and a previous study. The difference was probably attributable to birds being stressed while they were held in the metabolic chamber or wearing a mask. Thus, previous measurements of metabolic rate under basal conditions or for incubating wandering albatrosses are likely to be overestimates. Combining the relationship between HR and metabolic rate for both sexes, we estimate that wandering albatrosses expend 147 kJ kg(-1) day(-1) to incubate their eggs. In addition, the cost of incubation was assumed to vary because (i) HR was higher during the day than at night, and (ii) there was an effect of wind chill (<0 degrees C) on basal HR. The presence of humans in the vicinity of the nest or after a band control was shown to increase HR for extended periods (2-3 h), suggesting that energy expenditure was increased as a result of the disturbance. Lastly, males and females reacted differently to handling in terms of HR response: males reacted more strongly than females before handling, whereas females took longer to recover after being handled. (+info)
Loss of photic entrainment and altered free-running circadian rhythms in math5-/- mice.
Mammalian free-running circadian rhythms are entrained to the external light/dark cycle by photic signaling to the suprachiasmatic nuclei via the retinohypothalamic tract (RHT). We investigated the circadian entrainment and clock properties of math5-/- mutant mice. math5 is a critical regulator of retinal ganglion cell development; math5-/- mice show severe optic nerve hypoplasia. By anterograde cholera toxin B tracing, we find that math5-/- mice do not develop an identifiable RHT pathway. This appears to be attributable to agenesis or dysgenesis of the majority of RHT-projecting retinal ganglion cells. math5-/- mice display free-running circadian rhythms with a period approximately 1 hr longer than B6/129 controls (24.43 +/- 0.10 vs 23.62 +/- 0.19 hr; p < 0.00001). The free-running period of heterozygote mice is indistinguishable from that of controls. math5-/- mice show no entrainment to light/dark cycles, whereas heterozygote mice show normal entrainment to both 12 hr light/dark cycles and to a 1 hr skeletal photoperiod. math5-/- mice show reduced ability to entrain their rhythms to the nonphotic time cue of restricted running wheel access but demonstrate both free-running behavior and entrained anticipation of wheel unlocking in these conditions, suggesting the presence of a second diurnal oscillatory system in math5-/- animals. These results demonstrate that retinal ganglion cell input is not necessary for the development of a free-running circadian timekeeping system in the suprachiasmatic nucleus but is important for both photic entrainment and determination of the free-running period. (+info)
Rosuvastatin decreases caveolin-1 and improves nitric oxide-dependent heart rate and blood pressure variability in apolipoprotein E-/- mice in vivo.
BACKGROUND: Decreased heart rate variability (HRV) and increased blood pressure variability (BPV), determined in part by nitric oxide (NO)-dependent endothelial dysfunction, are correlated with adverse prognosis in cardiovascular diseases. We examined potential alterations in BPV and HRV in genetically dyslipidemic, apolipoprotein (apo) E-/-, and control mice and the effect of chronic statin treatment on these parameters in relation to their NO synthase (NOS)-modifying properties. METHODS AND RESULTS: BP and HR were recorded in unrestrained, nonanesthetized mice with implanted telemetry devices with or without rosuvastatin. Cardiac and aortic expression of endothelial NOS and caveolin-1 were measured by immunoblotting. Both systolic BP and HR were elevated in apoE-/- mice, with abolition of their circadian cycles. Spectral analysis showed an increase in their systolic BPV in the very-low-frequency (+17%) band and a decrease in HRV in the high-frequency (-57%) band, reflecting neurohumoral and autonomic dysfunction. Decreased sensitivity to acute injection of atropine or an NOS inhibitor indicated basal alterations in both parasympathetic and NOS regulatory systems in apoE-/- mice. Aortic caveolin-1 protein, an inhibitor of endothelial NOS, was also increased in these mice by 2.0-fold and correlated positively with systolic BPV in the very-low-frequency band. Rosuvastatin treatment corrected the hemodynamic and caveolin-1 expression changes despite persisting elevated plasma cholesterol levels. CONCLUSIONS: Rosuvastatin decreases caveolin-1 expression and promotes NOS function in apoE-/-, dyslipidemic mice in vivo, with concurrent improvements in BPV and HRV. This highlights the beneficial effects of rosuvastatin on cardiovascular function beyond those attributed to lipid lowering. (+info)
An abrupt shift in the day/night cycle causes desynchrony in the mammalian circadian center.
The suprachiasmatic nucleus (SCN) is the neuroanatomical locus of the mammalian circadian pacemaker. Here we demonstrate that an abrupt shift in the light/dark (LD) cycle disrupts the synchronous oscillation of circadian components in the rat SCN. The phases of the RNA cycles of the period genes Per1 and Per2 and the cryptochrome gene Cry1 shifted rapidly in the ventrolateral, photoreceptive region of the SCN, but were relatively slow to shift in the dorsomedial region. During the period of desynchrony, the animals displayed increased nighttime rest, the timing of which was inversely correlated with the expression of Per1 mRNA in the dorsomedial SCN. Molecular resynchrony required approximately 6 d after a 10 hr delay and 9 approximately 13 d after a 6 hr advance of the LD cycle and was accompanied by the reemergence of normal rest-activity patterns. This dissociation and slow resynchronization of endogenous oscillators within the SCN after an LD cycle shift suggests a mechanism for the physiological symptoms that constitute jet lag. (+info)
Loss of circadian rhythm of blood pressure following acute stroke.
BACKGROUND: Epidemiology of acute stroke in developing countries differs from that in the developed world, for example, the age at stroke, risk factors, subtypes of stroke and prognosis. Hypertension remains a dominant risk factor and prognostic indicator in patients with stroke in all communities. The risk of stroke is directly related to elevations of blood pressure. A number of clinical studies have shown that the control of hypertension leads to a reduction in the incidence of stroke in a community. However there is still considerable controversy surrounds the changes in blood pressure in various subtypes of strokes and problem of management of elevated BP after stroke. We studied the circadian rhythm of blood pressure in patients following acute stroke. METHODS: To study the circadian rhythm of blood pressure, fifty consecutive patients with an acute stroke who were admitted to medical emergency within 120 hours of onset were included in the study. After a detailed history and clinical examination, a continuous blood pressure monitor (Spacelab 90207) was attached on the side ipsilateral to intracranial lesion (unaffected arm). The blood pressure was recorded for 24 hours at 15 minutes interval during daytime (6.00 am-6.00 pm) and 20 minutes interval overnight (6 pm to 6 am). RESULTS: Risk factors for stroke in 50 patients included hypertension in 31(62%), diabetes mellitus in 4 (8%), smoking in 13 (26%) and previous history of transient ischemic attack in 7 (14%) patients. Mean systolic pressure and diastolic pressure at admission were higher in patients with hemorrhagic stroke -29 patients (177 +/- 24 mmHg and 105 +/- 19 mmHg respectively) compared to patients with ischemic strokes-21 patients (150 +/- 36 mm Hg and 89 +/- 18 mm Hg respectively, p value <0.01 in both comparisons). The normal diurnal variation in blood pressure (night time dipping of more than 10%) was abolished in 44 (88%) of patients. Out of 44 nondippers, 29 patients showed reverse dipping i.e. rise of BP during night time compared to day time levels. None of the risk factors, clinical or laboratory variables, type of stroke or blood pressure changes differed significantly between these two groups. CONCLUSIONS: Therefore, we showed a pathologically reduced or abolished circadian BP variation after stroke. Absence of normal dipping results in a higher 24 hour blood pressure load and may have more target organ damage than those with normal diurnal variation of blood pressure. (+info)